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Exosomal miR-155 from gastric cancer induces cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiation via C/EPBβ.

ABSTRACT:

Objective

The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia (CAC) by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer (GC)-associated adipocytes.

Methods

Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ, C/EPBα, PPARγ, and UCP1 in adipose mesenchymal stem cells (A-MSCs) to evaluate the function of exosomal miR-155. BALB/c nude mice were intravenously injected in vivo with GC exosomes with different levels of miR-155 to determine changes in adipodifferentiation of A-MSCs.

Results

Exosomes derived from GC cells suppressed adipogenesis in A-MSCs as characterized by decreased lipid droplets. Similarly, A-MSCs co-cultured with GC exosomes exhibited increased ATP production through brown adipose differentiation characterized by highly dense mitochondria and enhanced UCP1 expression (P < 0.05). Mechanistically, exosomal miR-155 secreted from GC cells suppressed adipogenesis and promoted brown adipose differentiation by targeting C/EPBβ, accompanied by downregulated C/EPBα and PPARγ and upregulated UCP1 (P < 0.05). Moreover, overexpression of miR-155 in GC exosomes improved CAC in vivo, which was characterized by fat loss, suppressed expressions of C/EPBβ, C/EPBα, and PPARγ in A-MSCs, and high expression of UCP1 (P < 0.05). Decreasing the level of miR-155 in injected GC exosomes abrogated the improved CAC effects.

Conclusions

GC exosomal miR-155 suppressed adipogenesis and enhanced brown adipose differentiation in A-MSCs by targeting C/EPBβ of A-MSCs, which played a crucial role in CAC.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9500219 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Exosomal miR-155 from gastric cancer induces cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiation <i>via</i> C/EPBβ.

Liu Ying Y Wang Meng M Deng Ting T Liu Rui R Ning Tao T Bai Ming M Ying Guoguang G Zhang Haiyang H Ba Yi Y

Cancer biology & medicine 20220201 9

<h4>Objective</h4>The aim of this research was to identify whether exosomes were involved in impairing adipogenesis in cancer-associated cachexia (CAC) by detecting the adipodifferentiation capacity and the expressions of adipogenic proteins in gastric cancer (GC)-associated adipocytes.<h4>Methods</h4>Western blotting and RT-PCR were used to investigate the expressions of C/EPBβ, C/EPBα, PPARγ, and UCP1 in adipose mesenchymal stem cells (A-MSCs) to evaluate the function of exosomal miR-155. BALB ...[more]

PMID: 35179324

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